The inability to achieve sufficient intratumoral concentrations of chemotherapeutic drugs in is one of the primary causes of treatment failure in patients with glioblastoma. We have shown in a Phase 1 clinical trial that a topoisomerase inhibitor, topotecan, can be safely and effectively delivered by convection enhanced delivery into patients with recurrent malignant gliomas as a means of overcoming systemic delivery limitations. In this proposal, we will improve this treatment strategy by validating an innovative method for non-invasive monitoring of drug distribution and expanding the duration of infusion by innovating the use of an implantable microinfusion pump. At the conclusion of these studies, the expected outcome will be a novel, measureable strategy to treat patients with recurrent glioblastoma via an implantable pump that can chronically deliver high doses of topotecan into the tumor and surrounding brain to avoid the limitations imposed by conventional systemic delivery. On a broader level, we will have demonstrated, for the first time in humans, the ability to chronically achieve a local-regional distribution of a drug directly into the brain parenchyma.

Public Health Relevance

Chemotherapy for brain tumors is ineffective because excessive side effects limit how much drug can be delivered into the brain. In our proposal we describe and critically test an innovative implantable catheter and pump system for delivering chemotherapy directly into the tumor for over extended time periods to avoid the side effects associated with standard oral or intravenous delivery.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA161404-01A1
Application #
8297366
Study Section
Developmental Therapeutics Study Section (DT)
Program Officer
Timmer, William C
Project Start
2012-07-01
Project End
2017-04-30
Budget Start
2012-07-01
Budget End
2013-04-30
Support Year
1
Fiscal Year
2012
Total Cost
$624,087
Indirect Cost
$229,319
Name
Columbia University (N.Y.)
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Sonabend, Adam M; Carminucci, Arthur S; Amendolara, Benjamin et al. (2014) Convection-enhanced delivery of etoposide is effective against murine proneural glioblastoma. Neuro Oncol 16:1210-9
Chow, D S; Qi, J; Guo, X et al. (2014) Semiautomated volumetric measurement on postcontrast MR imaging for analysis of recurrent and residual disease in glioblastoma multiforme. AJNR Am J Neuroradiol 35:498-503